In the clinical setting, it is a common observation that all fixed renal pelvic stones are adherent to the papilla (either the distal end of the ducts of Bellini, the renal papilla surface, or, less often, to the forniceal region). Stones are new found attached directly to the transitional epithelium of the papilla without ulceration and/or plaque. Once the stone dislodged from its' point of attachment, a site of eruption is noted in the transitional epithelium associated with the stone and that this site of eruption has, as its foundation or base, a plaque, termed a Randall's plaque after discovered. A clinical spectrum of papillary plaques is seen, from small subepithelial plaques to large, eroded plaques with a common association of attached calcium oxalate stones. The majority of the plaque area appears to be local beneath the transitional epithelium (subepithelial). Histologic examination of the affected papilla shows a region plaque extending into the interstitium of the papilla with additional regions of crystal deposition involving all tissues the papillary tip. The process by which a plaque forms is presently not known; however, it has been hypothesized (Anderson-Carr-Randall progression of renal calculus formation) that calcium deposits begin within the tissues of the papilla, which may migrate to a subepithelial position, forming Randall's plaques. The uniqueness of the experimental design of this project is that we will undertake this study in kidneys of well-characterized human stone formers using the technical advances that have occurred in endoscopic equipment and percutaneous surgical techniques. Such approach has not been previously used to study the pathogenesis of uroliathiasis. Tissue samples will be collected from all regions of the kidney and analyzed using crystallography, Fourier transform infrared microscopy and spectroscopy quantitatively energy and wavelength dispersive analysis, light; transmission and scanning electron microscopy. The morphological/analytical data will then be correlated with physiologic data (serum and urine studies) collected from patients. Within the construct of a cooperative program project, we plan to determine what are the important a substantive steps that lead to pathologic formation of uroliathiasis. The other projects will address urinary metabolic factors and crystal inhibitors (Project 1), hypercalciuria in an animal model (Project 3), vitamin D physiology (Project 4) and crystal-cell interactions, growth and inhibitions (Project 5).